In recent years, significant effort has been devoted to develop nanotechnology for drug delivery since it offers a suitable means of delivering small molecular weight drugs, as well as macromolecules such as proteins, peptides or genes by either localized or targeted delivery to the tissue of interest. Nanotechnology focuses on formulating therapeutic agents in biocompatible nanocomposites such as nanoparticles, nanocapsules, micellar systems, and conjugates. Protein nanoparticles (BSA, HAS and gelatin) generally vary in size from 20-500 nm and they hold certain advantages such as greater stability during storage, stability in vivo, non-toxicity, non-antigen and ease to scale up during manufacture over the other drug delivery systems. The primary structure of gelatin offers many possibilities for chemical modification and covalent drug attachment, e.g. for drug delivery in general, and as an injectable drug delivery system in particular.
Some fractures heal only slowly due to complexity of the fracture or because the patient has a retarded growth. Current methods to accelerated growth make use of a growth factor bounded to tissue, e.g. collagen. This method activates bone cells to activate growth. Existing methods are based on filling the fracture with granulate material from natural or synthetic resources. This requires invasive surgery, which is demanding for the patient.
Another more preferred option is to use injectable materials. For example, U.S. Pat. No. 5,932,245 discloses a dosage formulation that provides for the release of nanoparticles. It comprises (a) an inner phase that comprises at least one nanoparticle compound; and (b) an outer phase that comprises a compound selected from the group consisting of gelatin, collagen hydrolyzates and mixtures thereof. The preferred nanoparticle size is in the range from 10-800 nm. Glibenclamide is mentioned as the nanoparticle compound for treatment of diabetes.
US 2008/0003292 discloses nanoparticles, essentially consisting of an aqueous gelatin gel, wherein the nanoparticles have an average diameter of at most 350 nm and polydispersity index of less than or equal to 0.15. The nanoparticles are used as carrier systems for medical substances. This publication deals with the problem of broad size distribution of nanoparticles which is disadvantageous with a view to a uniform release and transport behavior. In the examples, gelatin is dissolved in water and pH value is adjusted. The de-solvation of the gelatin is carried out by way of the drop by drop addition of acetone. Aqueous glutaric aldehyde solution is added. The nanoparticles cross-linked in this way are separated from the solution.
The known processes for making gelatin nanoparticles are difficult to control.